Hearing in humans requires conduction of the acoustic signal to the inner ear by way of the external auditory canal, tympanic membrane, and ossicles (i.e., malleus, incus, and stapes). Vibration of the stapes bone (i.e., the 3rd ossicle) within the oval window of the inner ear sets the inner ear fluids in motion thereby inducing activation of hair cells in the cochlea. Hair cell activation results in cochlear nerve fiber depolarization, ultimately leading to central auditory pathway stimulation within the brainstem.
Hearing impairments can be classified as either conductive, resulting from pathologies of the external auditory canal, tympanic membrane, and/or ossicles, or sensorineural. Sensorineural hearing losses (SNHL) most commonly result from either hair cell loss within the cochlea or as a consequence cochlear nerve disorders. By far, the most common factor for SNHL is hair cell loss. Although hair cell losses can occur throughout the cochlea, the most commonly involved regions are the high frequency (high pitch) regions.
The cochlea has a tonotopical arrangement, which means that tones close to each other in terms of frequency are received by hair cells in topologically neighboring regions of the cochlea (FIG. 1). In general, hair cells in the basal region (base) of the cochlea are activated by high frequency sound, and hair cells in the apical region (apex) of the cochlea are activated by low frequency sound. As such, hair cell losses occur most commonly in the basal regions of the cochlea, resulting in high frequency hearing impairment.
Effective hearing impairment treatment necessitates accurate determination of the cause and/or extent of hearing impairment. For example, to provide an effective and specific treatment for a hearing impairment, it is desirable to determine whether hearing impairment is conductive or sensorineural, and if sensorineural, whether it is a result of hair cell loss or neural disorder. Further, if hearing impairment results from loss of hair cell function, it would be desirable to determine the topological extent of hair cell loss to better tailor a treatment specifically for the hearing deficit. Present technologies for measuring hearing impairment are unable to provide a complete and accurate determination of the cause and/or extent of hearing impairment, particularly with regard to assessment of hair cell function.
Site of lesion testing within the auditory system is indirect, as cochlear and central nervous system biopsy is both impractical and would result in hearing loss. Present methods for measurement of hair cell function include evoked-otoacoustic emissions (OAEs) (Kemp, 1986), auditory brainstem response (ABR) testing, and behavioral audiograms. For almost 20 years, otoacoustic emissions (measure of hair cell motion and resultant sound from the hair cell motion) have been relied upon to provide information about the functional status of the inner ear. Due to the specificity of OAEs for outer hair cells, this technique can be sensitive in the early diagnosis of hair cell pathology. However, beyond about 40 decibels (dB) of hearing loss, OAEs are lost, making further assessment impossible. Moreover, the recording mechanism relies on several factors outside the inner ear, making OAE testing both indirect and inaccurate during times of pathology.
Another way to potentially evaluate hair cell function is to record ABR after stimulating the cochlea acoustically through a microphone in the external auditory canal. The electrical activity of the auditory pathways is recorded and filtered from the electrical activity of the brain. The earliest electrical potentials observed with this method are termed the cochlear microphonic potential. The cochlear microphonic potential is a measure of summated inner ear hair cell function and thus can provide some information about the overall functional status of the cochlea. ABR recordings, however, are recorded via far field electrodes mounted on the scalp of the subject. Using this method, the electrical responses of the cochlear microphonics are buried in the much stronger electrical activity of the auditory nerve (compound action potential). Usually, only in special cases where the auditory nerve fires in a dys-synchronous manner do cochlear microphonics become evident in the far field recordings. Moreover, since the cochlear microphonic potential is an averaged and summated vector potential, measurements from the various anatomic regions within the cochlea to determine the extent and range of hearing impairment are not possible with this technique.
Other recording sites for auditory potentials are the external auditory canal and the surface of the promontory in the middle ear. In contrast to far-field electrodes mounted on the scalp of the subject, these recording sites provide a better signal-to-noise ratio and can furnish greater response amplitudes at the same stimulus intensity levels, facilitating the recording of much smaller responses. Since two main electrical potentials, the cochlear microphonic (stemming from hair cells) and the compound action potential (summation potential from spiral ganglion cells as the first neural response), are recorded, this technique has been termed electrocochleography (ECochG). Due to the close anatomic relationship of the basal cochlear turn and the recording sites in the external auditory canal or the promontory, the cochlear microphonic potential is believed to be mainly a result of basal cochlear hair cells with a negligible fraction of apical hair cell contribution. Thus, this technique does not allow for measurement of apical hair cell function.
Present methods for measuring hearing deficiency, and specifically for measuring hair cell functionality, are insufficient to meet the needs of specific and accurate measurement of hair cells. As such, there is an unmet need for direct and accurate measurement of acoustically or mechanically stimulated electrophysiologic activity.